Pixantrone (BBR 2778 (free base)) hydrochloride is a mitoxantrone analog compound that acts as a topoisomerase II inhibitor and DNA intercalator. It displays anti-tumor activity [1] [2].

Pixantrone (0-10 μM, 72 h) hydrochloride induces cell death in multiple cancer cell lines independent of cell cycle perturbation [1]. Pixantrone (25-500 nM, 24 h) hydrochloride can induce DNA damage, hinder chromosome segregation, and induce severe chromosomal aberrations and mitotic catastrophes in PANC1 cells [1]. Pixantrone (0-100 μM, 72 h) hydrochloride potently inhibits growth of human leukemia K562 cells, etoposide-resistant K/VP.5 cells, MDCK and ABCB1-transfected MDCK/MDR cells with IC 50 s of 0.10 μM, 0.56 μM, 0.058 μM and 4.5 μM, respectively [2]. Pixantrone (0.01-0.2 μM) hydrochloride leads to a concentration-dependent formation of linear DNA through acting on topoisomerase IIα and produces semiquinone free radicals in an enzymatic reducing system, although not in a cellular system, most likely due to low cellular uptake [2]. Pixantrone (0.01-10 μM) hydrochloride shows potent inhibitory activities against rat 97-116 peptide-specific T cell proliferation [4]. Cell Proliferation Assay [1] Cell Line: T47D, MCF-10A and OVCAR5 cells Concentration: 0-10 μM Incubation Time: 72 h Result: Reduced the proliferation of T47D, MCF-10A and OVCAR5 cells with 37.3 nM, 126 nM and 136 nM, respectively. Cell Proliferation Assay [4] Cell Line: Lewis rat T cell lines Concentration: 0.01-10 μM Incubation Time: Result: Inhibited 39.3% rat 97-116 peptide-specific T cells proliferation at 0.01 μM and completely suppressed T cell proliferation at high concentrations.

Pixantrone (i.v., 27 mg/kg, every 7 days, three times) hydrochloride does not worsen pre-existing moderate degenerative cardiomyopathy, causes minimal cardiotoxic in mice following repeated treatment cycles and results in less mortality than mitoxantrone in doxorubicin-pretreated mice [3]. Pixantrone (i.v., 16.25 mg/kg, every week, three times) hydrochloride modulates Lymph node cells (LNC) responses, affacts T cell subpopulations in TAChR-immunized Lewis rats and also shows preventive and therapeutic effect in experimental autoimmune myasthenia gravis (EAMG) rats [4].